3vw7: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of human protease-activated receptor 1 (PAR1) bound with antagonist vorapaxar at 2.2 angstrom== | ==Crystal structure of human protease-activated receptor 1 (PAR1) bound with antagonist vorapaxar at 2.2 angstrom== | ||
<StructureSection load='3vw7' size='340' side='right' caption='[[3vw7]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='3vw7' size='340' side='right' caption='[[3vw7]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| Line 5: | Line 6: | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=VPX:ETHYL+[(1R,3AR,4AR,6R,8AR,9S,9AS)-9-{(E)-2-[5-(3-FLUOROPHENYL)PYRIDIN-2-YL]ETHENYL}-1-METHYL-3-OXODODECAHYDRONAPHTHO[2,3-C]FURAN-6-YL]CARBAMATE'>VPX</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=VPX:ETHYL+[(1R,3AR,4AR,6R,8AR,9S,9AS)-9-{(E)-2-[5-(3-FLUOROPHENYL)PYRIDIN-2-YL]ETHENYL}-1-METHYL-3-OXODODECAHYDRONAPHTHO[2,3-C]FURAN-6-YL]CARBAMATE'>VPX</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vw7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vw7 RCSB], [http://www.ebi.ac.uk/pdbsum/3vw7 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vw7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vw7 OCA], [http://pdbe.org/3vw7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vw7 RCSB], [http://www.ebi.ac.uk/pdbsum/3vw7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vw7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 17: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3vw7" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 12:15, 4 August 2016
Crystal structure of human protease-activated receptor 1 (PAR1) bound with antagonist vorapaxar at 2.2 angstromCrystal structure of human protease-activated receptor 1 (PAR1) bound with antagonist vorapaxar at 2.2 angstrom
Structural highlights
Function[PAR1_HUMAN] High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation and in vascular development.[1] Publication Abstract from PubMedProtease-activated receptor 1 (PAR1) is the prototypical member of a family of G-protein-coupled receptors that mediate cellular responses to thrombin and related proteases. Thrombin irreversibly activates PAR1 by cleaving the amino-terminal exodomain of the receptor, which exposes a tethered peptide ligand that binds the heptahelical bundle of the receptor to affect G-protein activation. Here we report the 2.2 A resolution crystal structure of human PAR1 bound to vorapaxar, a PAR1 antagonist. The structure reveals an unusual mode of drug binding that explains how a small molecule binds virtually irreversibly to inhibit receptor activation by the tethered ligand of PAR1. In contrast to deep, solvent-exposed binding pockets observed in other peptide-activated G-protein-coupled receptors, the vorapaxar-binding pocket is superficial but has little surface exposed to the aqueous solvent. Protease-activated receptors are important targets for drug development. The structure reported here will aid the development of improved PAR1 antagonists and the discovery of antagonists to other members of this receptor family. High-resolution crystal structure of human protease-activated receptor 1.,Zhang C, Srinivasan Y, Arlow DH, Fung JJ, Palmer D, Zheng Y, Green HF, Pandey A, Dror RO, Shaw DE, Weis WI, Coughlin SR, Kobilka BK Nature. 2012 Dec 20;492(7429):387-92. doi: 10.1038/nature11701. Epub 2012 Dec 9. PMID:23222541[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Human
- Lysozyme
- Arlow, D H
- Coughlin, S R
- Dror, R O
- Fung, J J
- Green, H F
- Kobilka, B K
- Palmer, D
- Pandey, A
- Shaw, D E
- Srinivasan, Y
- Weis, W I
- Zhang, C
- Zheng, Y
- Antagonist vorapaxar
- G protein-coupled receptor
- High resolution structure
- Inactive conformation
- Membrane protein
- Protease-activated receptor 1
- Signaling protein
- Signaling protein-antagonist complex
- Thrombin receptor-antagonist complex